title: Extending fragment-based free energy calculations with library Monte Carlo simulation: annealing in interaction space.
abstract: Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via library-based Monte Carlo) and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all-atom poly-alanine systems in a simple dielectric solvent and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor time is required. The combined approach is formally equivalent to the annealed importance sampling algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is grown. We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site.
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Lettieri
authors.forename: Artem B
authors.initials: AB
authors.lastname: Mamonov
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Zuckerman
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D008024:Ligands; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D011789:Quantum Theory; D013696:Temperature
chemical_list: D008024:Ligands; D010455:Peptides; C019529:polyalanine